This study is designed to determine the relationship between the binding of thyroid hormones to nuclear and cytoplasmic binding proteins and the change in gene transcription which are induced by the thyroid hormones using the tadpole as a model system. The binding will be measured in two tissues, the liver and tail fin, which undergo vastly different alterations during metamorphosis. The initial phase of the proposed work is to measure the dissociation constant and number of binding sites for triiodothyronine and the relative binding of various thyroid hormone analogues to nuclei isolated from livers and tail fins of Rana catesbeiana tadpoles and compare the results with previous tests performed on the binding to cytoplasmic proteins. The number of binding sites and dissociation constant for the binding of triiodothyronine will then be measured throughout metamorphosis to determine if there is synthesis of new binding proteins as the circulating levels of hormone increase. The physiochemical properties of the cytoplasmic and nuclear binding proteins for thyroid hormones will also be analyzed by sucrose gradient centrifugation, Sephadex gel chromatography, and disc gel electrophoresis to provide further insight into their similarities and differences. A further aspect of the proposed work will be to investigate the possibility that a thyroid hormone-cytoplasmic binding protein complex serves to transfer thyroid hormones to the nucleus. These studies will serve to advance our understanding of the mechanism by which thyroid hormones control growth and differentiation. BIBLIOGRAPHIC REFERENCES: S.H. Socher, J.F., Krall, R.C. Jaffe, and B.W. O'Malley, "Distribution of binding sites for the progesterone receptor within chick oviduct chromatin" Endocrinology 99: 891-900, 1976. R.C. Jaffe, S.H. Socher, and B.W. O'Malley, "An analysis of the binding of the chick oviduct progesterone-receptor to chromatin" Biochem Biophys Acta 399: 403-419, 1975.